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. 2022 May 25:12:767750.
doi: 10.3389/fonc.2022.767750. eCollection 2022.

LncRNAs as Theragnostic Biomarkers for Predicting Radioresistance in Cancer: A Systematic Review and Meta-Analysis

Ping Lin  1 , Wenmin Xing  2 , Qian Ren  1 , Qin Wang  1 , Jing Yan  2 , Genxiang Mao  2
Affiliations

LncRNAs as Theragnostic Biomarkers for Predicting Radioresistance in Cancer: A Systematic Review and Meta-Analysis

Ping Lin et al. Front Oncol. .

Abstract

Background: Radioresistance is the major obstacle after cancer radiotherapy. The dysregulation of long non-coding RNAs (lncRNAs) was closely related the radioresistance response. This meta-analysis was aimed to interpret the relationship between lncRNAs and radiotherapy responses in different cancers.

Method: The studies were selected from databases including PubMed, ISI Web of Science, Embase, Google Scholar, PMC, and CNKI (China National Knowledge Infrastructure). The publication time was limited to before March 20, 2021. The hazard ratios (HRs) and 95% confidence interval were calculated with random-effects models. Subgroup analyses, sensitivity analyses, and publication bias were also conducted.

Result: Twenty-seven lncRNAs in 14 cancer types were investigated, in which 23 lncRNAs were upregulated and four lncRNAs were downregulated. Dysregulation of these lncRNAs were found to be related to radioresistance response. The pooled HR and 95% confidence interval for the combined up-regulated lncRNAs was 1.73 (95% CI=1.50-2.00; P< 0.01) and down-regulated lncRNAs was 2.09 (95% CI= 1.60-2.72; P< 0.01). The HR values of the subgroup analysis for glioma (HR= 2.22, 95% CI= 1.79-2.74; p< 0.01), non-small cell lung cancer (HR=1.48, 95% CI=1.18-1.85; P<0.01), nasopharyngeal carcinoma (HR=4.26; 95% CI= 1.58-11.46; P< 0.01), and breast cancer (HR=1.29; 95% CI= 1.08-1.54; P< 0.01) were obtained. Moreover, the expression of lncRNAs was significantly related to overall survival of patients no matter if the sample size was >50 or not. In addition, the HR values of the subgroup analysis for lncRNA H19 (HR=2.68; 95% CI= 1.92-3.74; P <0.01), lncRNA FAM201A (HR=2.15; 95% CI= 1.15-3.99; P <0.01), and lncRNA HOTAIR (HR=1.22; 95% CI= 0.98-1.54; P =0.08) were also obtained.

Conclusion: LncRNAs can induce cancer radioresistance by regulating cell death-related signaling pathways. Results indicated that lncRNAs, especially lncRNA H19, FAM201A, and HOTAIR, could be considered as a predictive theragnostic biomarker to evaluate radiotherapy response.

Keywords: cancer; long non-coding RNAs; meta-analysis; radioresistance; theragnostic biomarkers.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
The diagram flowchart of studies for selecting process.
Figure 2
Figure 2
The interaction network of targets protein and gene function prediction of lncRNAs pathways involved in radiosensitivity. (A) The interaction network of targets protein of lncRNAs from STRING database (https://www.string-db.org/). (B) Coexpression scores based on RNA expression patterns, and on protein co-regulation provided by STRING. (C) Gene network of enriched terms by Metascape (https://metascape.org/), a subset of enriched terms has been selected and rendered as a network plot, where terms with a similarity > 0.3 are connected by edges. We select the terms with the best p-values from each of the 20 clusters, with the constraint that there are no more than 15 terms per cluster and no more than 250 terms in total, where each node represents an enriched term.
Figure 3
Figure 3
Forest plot for the association between the lncRNAs expression levels with OS. (A) Subgroup analysis of the association between lncRNAs expression level and cancer patients according to the up-regulation and down-regelation of lncRNAs. (B) Subgroup analysis of the association between lncRNAs expression level and cancer patients according to the difference of cancer types. (C) Subgroup analysis of the association between lncRNAs expression level and cancer patients according to the difference of samples size. (D) Subgroup analysis of the association between different lncRNAs expression level and the OS of cancer patients. OS, overall survival.
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